Organic Reaction Studies by ESI‐MS

Abstract

IntroductionReactions are the heart and soul of chemistry. Therefore chemists, to effectively control and improve their chemical reactions, need to know the mechanistic details by which these usually sophisticated, multistep and multicomponent processes with many intermediates and transient species proceed. The tremendous success and rapid broad use of electrospray ionization mass spectrometry (ESI-MS) [1] results mainly from its ability to transfer, in a gentle and efficient way, ions of many types, charge states and nearly unlimited masses from the real-world environment of reaction solutions directly to the diluted gas phase and to characterize these intact and isolated gaseous ions according to their masses and connectivities with the outstanding speed, sensitivity and selectivity that only mass spectrometry is able to provide. ESI-MS (for ion detection and mass and isotopic pattern determination) as well as its tandem version ESI-MS(/MS) (for structural investigation) has therefore established itself as the principal technique to study reaction mechanisms of organic reactions in solution. ESI can fish, rapidly and efficiently, reactants, intermediates and products (either ionic species or molecules in ionic forms) and transfer them to mass spectrometers (leaving behind the solvent molecules and counter ions) to measure their masses and access their structures and intrinsic reactivities using tandem MS/MS experiments. Continuous on-line monitoring of organic reactions of many types by ESI-MS(/MS) ion fishing (Figure 3.1) provides instantaneous and comprehensive snapshots of the ionic composition and thus permits organic chemists to follow how these reactions progress as a function of time and reaction conditions, whereas the high sensitivity and speed of ESI-MS allow even transient (low concentrations for short times) intermediates to be detected and characterized. The intrinsic reactivity of each key gaseous species fished by ESI can also be further investigated via ESI-MS(/MS) experiments in the search for the most intrinsically active species via gas-phase ion/ molecule reactions in which solvent and counter-ion effects are absent. Therefore, the ability to fish ions (or neutral, zwitterionic, or radical species in ionic forms such as protonated, deprotonated, or cationized or anionized molecules) provides a detailed j63 64j 3 Organic Reaction Studies by ESI-MS R 1 OH Scheme 3.2 Currently accepted catalytic cycle for the MBH reaction. 3.2 Reaction Mechanisms j65 66j 3 Organic Reaction Studies by ESI-MS À , CF 3 CO 2 À ). 68j 3 Organic Reaction Studies by ESI-MS 70j 3 Organic Reaction Studies by ESI-MS 98j 3 Organic Reaction Studies by ESI-MS

Mechanism of Palladium(II)-Mediated Uncaging Reactions of Propargylic Substrates

“…Continuing with the aim to unveil the nature of the catalytic species, high-resolution electrospray ionization mass spectrometry (ESI–HRMS) was used to monitor the reaction and possible detection of key reaction intermediates. − ESI is a soft ionization technique that can be used to analyze both cations and anions, displays high sensitivity, and allows the immediate transfer to the gas phase of most ionic species present in the reaction solution. Working in negative ion mode, the in situ ESI(−)–HRMS monitoring of the reaction, with 20 mol % of Na 2 PdCl 4 in phosphate-buffered aqueous solution pH 7.4 (5% DMSO) provided 10 min after the start of the reaction, identified the following proposed species: the product DNP ( m / z = 183) as the major species (Figure a) and three other Pd species interacting with the substrate at m / z 434.8, 416.9, and 638.9 (Figure b–d).…”

Catalytic intramolecular carbonyl–ene reaction with ketones: evidence for a retro–ene process

“…In particular, this would be of interest in characterizing organometallic intermediates with their entire coordination sphere. 26 Recently, several MS studies yielded detailed information about elementary reaction steps of important reactions 27 such as the Heck 28,29 or the Stille coupling, 30 the Baylis-Hillman, [31][32][33][34] or the Biginelli reactions [35][36][37] or some gold-catalyzed reactions. 38,39 Fig.…”

Insight into the Mechanisms of the Multicomponent Ugi and Ugi–Smiles Reactions by ESI‐MS(/MS)

“…In this context, the “soft” electrospray ionization occupies a prominent position as interface between the ions and ionizable species existing in solution and those observed in the gas phase. Several MS studies yielded detailed information about the elementary steps of important reactions such as the Heck, Stille, Baylis–Hillman,11 and Biginelli reactions 12. We reasoned, however, that the presence of an ionic hook in every intermediate/transition state might constitute a bias on the reaction pathway by altering the reaction thermodynamics and kinetics.…”