Krista L. Vikse

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.

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.

Cobalt-Mediated Decarboxylative Homocoupling of Alkynyl Carboxylic Acids

Cobalt-mediated decarboxylative Glaser-like C–C bond coupling of carboxylates has been studied in the gas phase using collision-induced dissociation (CID) multistage mass spectrometry (MSn) experiments. Both the identity of the carboxylate RCO2– (R = Me, HC≡C, MeC≡C, and PhC≡C) and the nuclearity of the complex ([CoCl(O2CR)2]– versus [Co2Cl3(O2CR)2]–) play a role in the types of reactions observed and their relative activation energies. In the first stage of CID, the mononuclear complex [CoCl(O2CMe)2]– undergoes decarboxylation, while the dinuclear [Co2Cl3(O2CMe)2]– undergoes cluster fission to yield [CoCl3]–; all acetylenic carboxylate complexes [CoCl(O2CR)2]– and [Co2Cl3(O2CR)2]– undergo decarboxylation. Isolation of the decarboxylated products followed by a second stage of CID results in a second decarboxylation event for all systems except for [CoCl(Me)(O2CMe)]–, which undergoes bond homolysis. In the final stage of CID, all acetylenic complexes undergo Glaser coupling, forming reduced Co anions. Overall dinuclear cobalt clusters are superior to mononuclear complexes at promoting decarboxylation and reductive coupling. The order of reactivity among the acetylide ligands is PhC≡C > MeC≡C > HC≡C.

Mechanistic insights from mass spectrometry: examination of the elementary steps of catalytic reactions in the gas phase

Abstract 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.

Ionization methods for the mass spectrometry of organometallic compounds

The rapid development of new ionization methods has greatly expanded the ability of mass spectrometry to target diverse areas of chemistry. Synthetic organometallic and inorganic chemists often find themselves with interesting characterization problems that mass spectrometry could potentially find the answer for, but without a guide for choosing the appropriate method of analysis. This tutorial review seeks to provide that guidance via a simple flow chart followed by a brief description of how each common ionization method works. It covers all of the commonly used ionization techniques as well as promising variants and aims to be a resource of first resort for organometallic chemists and analysts tackling a new problem.