J. Scott McIndoe

Powerful Insight into Catalytic Mechanisms through Simultaneous Monitoring of Reactants, Products, and Intermediates

Electrospray ionization mass spectrometry (ESIMS) has become a valuable tool in the mechanistic study of organometallic catalytic reactions. Analysis is fast, intermediates at low concentrations can be detected, and complex mixtures are tractable. The family of palladium-catalyzed C C bondforming reactions are the most studied by ESIMS. Although the majority of these investigations have focused on the structural identification of short-lived or low-concentration intermediates, some recent studies have monitored the intensities of intermediates or reactants and products over time. 14] However, no one has yet shown this technique to be capable of providing robust kinetic information for reactants, products, by-products, and low-abundance intermediates simultaneously and under standard reaction conditions. We show herein how powerful this information can be in leading reaction design. The copper-free Sonogashira (Heck alkynylation) reaction is widely used in the synthesis of natural products, pharmaceuticals, and novel materials, but the mechanism is not well understood. Ideally, the reaction should be observed under typical reaction conditions for meaningful information to be obtained about the mechanism, because under such conditions anions and bases 18] as well as alkynes are thought to act as ligands for palladium, with complex effects on the reaction efficiency. In most cases, a large excess of an amine base is required to promote reaction; however, the exact role of the base is in question. Dieck and Heck and Amatore et al. suggested a carbopalladation mechanism in which the terminal alkyne undergoes carbopalladation and the base consumes the H formed during the b-hydride elimination that forms the product. Ljundahl et al. prefer a deprotonation mechanism in which deprotonation of the terminal alkyne by the amine occurs from the cationic intermediate [Pd(Ar)(PR3)(NR’3)(HC CR’’)] or the neutral intermediate [Pd(Ar)(PR3)(X)(HC CR’’)], depending on the electronic nature of the alkyne. An anionic mechanism has also been proposed in which [Pd(PR3)2X] and [Pd(PR3)(X)(Ar)(CCR’’)] intermediates feature. The identity of palladium-containing intermediates has been proposed on the basis of electrochemical or NMR spectroscopic data but not through direct observation. Charged tags are required for the detection of species otherwise invisible to ESIMS, 24] an idea first introduced by Adlhart and Chen; we used an aryl iodide functionalized with a phosphonium hexafluorophosphate salt, [p-IC6H4CH2PPh3] [PF6] . This tag provides very low detection limits owing to its high surface activity, and the noncoordinating counterion reduces ion pairing. The bulky nature of the charged group ensures that the ionization efficiency is largely insensitive to the remaining structure of the ion, so the intensity of the various ions correspond very closely to their real concentration (see the Supporting Information). ESIMS data on reaction progress collected under typical reaction conditions by using pressurized sample infusion (PSI) compare well with H NMR and UV/Vis spectroscopic data (Figure 1). The number of data points is much higher for

Oxidative Additions of Aryl Halides to Palladium Proceed through the Monoligated Complex

Palladium(0) complexes facilitate many catalytic transformations that begin with the oxidative addition of a halobenzene. The ligation state of the palladium during this reaction is a vexing issue, owing to the inherent difficulty of isolating reactive, coordinatively unsaturated metal complexes. By isolating them in the gas phase in an ion‐trap mass spectrometer, the reactivity of mono‐ and bisligated palladium complexes can be directly compared, and the former proved to be several orders of magnitude more reactive towards halobenzenes. Calculations of barrier heights for the oxidative addition led to additional experiments, which demonstrated that although the reaction proceeded to completion for iodobenzene, the reaction was slower for bromobenzene and progressed only as far as an ion–molecule adduct for chloro‐ and fluorobenzene.

Energy-dependent electrospray ionisation mass spectrometry: applications in transition metal carbonyl chemistry

Maps of electrospray mass spectrometry data, plotted as cone voltage versus mass-to-charge ratio, provide a clear and compact method of visualising the accompanying fragmentation processes, in this case applied to the sequential removal of ligands from transition-metal carbonyl complexes. The technique is described as energy-dependent electrospray ionisation mass spectrometry (EDESI-MS). Copyright 2000 John Wiley & Sons, Ltd.

Mass spectrometric identification of singly-charged anionic and cationic sulfur, selenium, tellurium and phosphorus species produced by laser ablation

Laser desorption/ionisation mass spectrometry of the elements sulfur, selenium, tellurium and phosphorus has shown a range of polynuclear ions in both positive and negative ion modes. Three-dimensional topographical surfaces are used to display changes in the speciation of sulfur ions with increasing laser power under laser desorption/ionisation conditions, using a technique described as energy-dependent laser desorption/ionisation mass spectrometry; the positive and negative ion spectra of sulfur are both dominated by singly-charged ions, with S5 and S3 showing particular intensity. Similar results are also reported for the other title elements. # 2002 Elsevier Science B.V. All rights reserved.

Synthesis and characterization of a new class of anti-angiogenic agents based on ruthenium clusters

New triruthenium-carbonyl clusters derivatized with glucose-modified bicyclophosphite ligands have been synthesized. These compounds were found to have cytostatic and cytotoxic activity and depending on the number of bicyclophosphite ligands, and could be tuned for either anti-cancer or specific anti-angiogenic activity. While some compounds had a broad cellular toxicity profile in several cell types others showed endothelial cell specific dose-dependent anti-proliferative and anti-migratory efficacy. A profound inhibition of angiogenesis was also observed in the in vivo chicken chorioallantoic membrane (CAM) model, and consequently, these new compounds have considerable potential in drug design, e.g. for the treatment of cancer.

Mass spectrometric and theoretical study of polyiodides: the connection between solid state, solution, and gas phases.

Polyiodides have been transferred intact from acetonitrile solution to the gas phase and analyzed by mass spectrometry. A range of ions were observed, including [I(11)](-), [I(13)](-), and [I(15)](-), which have higher iodine/iodide ratios than any previously characterized ions. Theoretical calculations show that branched structures are strongly favored, a result which is in excellent agreement with with gas phase fragmentation studies (MS/MS) and also previous solid state studies. This study demonstrates the utility of mass spectrometry to provide structural information in the absence of other spectroscopic handles.

Direct probe electrospray (and nanospray) ionization mass spectrometry of neat ionic liquids

Electrospray ionization mass spectrometry of neat ionic liquids does not require continuous sample injection and the presence of a molecular solvent facilitates analysis of the ionic liquid itself and dissolved analytes.

A mechanistic investigation of hydrodehalogenation using ESI-MS†

The rate of hydrodehalogenation of aryl iodides with a palladium catalyst in methanol exhibits a strong primary kinetic isotope effect from both CD3OD and CH3OD, suggesting that deprotonation plays a major role in the mechanism.

Collision-induced dissociation and photodetachment of singly and doubly charged anionic polynuclear transition metal carbonyl clusters: Ru3Co(CO)13−,Ru6C(CO)162−, and Ru6(CO)182−

Three polynuclear transition metal carbonyl cluster anions, Ru3Co(CO)13−, Ru6C(CO)162−, and Ru6(CO)182− have been studied using energy-dependent electrospray ionization mass spectrometry (EDESI–MS) and photodetachment photoelectron spectroscopy (PES). EDESI–MS maps show a simple collision-induced dissociation (CID) process for Ru3Co(CO)n− by stripping CO down to the metal core. For the doubly charged species, two competing CID channels were observed, viz. loss of neutral CO and loss of CO+e−. It was found that the parent dianions first lose neutral CO down to n=9, producing a series of dianions, Ru6C(CO)n2− (n=9–16) and Ru6(CO)n2− (n=9–18). For n<9, the dianions become electronically unstable against autodetachment, and singly charged anions, Ru6C(CO)n− and Ru6(CO)n− (n=0–9), were observed. The PES spectra of the dianions show the electron binding energies decrease monotonically as n decreases and become ∼0.0 eV for n=9, in exact agreement with the CID patterns that reflect the electronic instability of t...

Facile cleavage of Si-Si or Si-Ge bonds in the reactions of disilanes or germylsilanes with cobalt carbonyl

The disilane (Ph2HSi)2 reacted at room temperature with Co2(CO)8 to yield Co(SiPh3)(CO)4 as a major product. Corresponding monosilyl derivatives were formed also when other disilanes Ph3SiSiR2 H( R 2 Ph2, PhMe, Me2 ,E t 2), Me3SiSiPh2H and PhMe2SiSiPhMeH were reacted with Co2(CO)8 under the same conditions. A mechanism based on silyl‐silylene intermediates is proposed. The germylsilanes Ph3GeSiR2 H( RPh, Et) with Co2(CO)8 also gave Co(SiPh3)(CO)4 by selective elimination of:GePh2 which was trapped by Co2(CO)8 as Ph2Ge[Co(CO)4]2. Crystal structures of Co(SiPh3)(CO)4 and Ph2Ge[Co(CO)4]2 are presented.