Applications of Electrospray Ionization Mass Spectrometry in Mechanistic Studies and Catalysis Research

Abstract

Mechanistic studies form the basis for a better understanding of chemical processes, helping researchers develop more sustainable reactions by increasing the yields of the desired products, reducing waste production, and lowering the consumption of resources and energy overall. Conventional methods for the investigation of reaction mechanisms in solution include kinetic studies, isotope labeling, trapping of reactive intermediates, and advanced spectroscopic techniques. Within the past decade, electrospray ionization mass spectrometry (ESI-MS) has provided an additional tool for mechanistic studies because researchers can directly probe liquid samples by mass spectrometry under gentle conditions. Specifically, ESI-MS allows researchers to identify the molecular entities present in solution over the course of a chemical transformation. ESI-MS is particularly useful for investigations of organic reactions or metal catalysis that involve ionic intermediates. Accordingly, researchers are increasingly using ESI-MS in mechanistic studies and catalyst development. However, a further understanding of the ESI process and how it can facilitate mechanistic studies has not accompanied this increased use of the technique. Therefore, at least in part the ESI-MS method not only has offered great promise for the elucidation of reaction mechanisms but also became a black box with the occasional risk of misinterpretation. In this Account, we summarize applications of ESI-MS for synthetic and mechanistic research. Recently researchers have established direct linkages between gas-phase data obtained via ESI-MS and processes occurring in solution, and these results reveal qualitative and quantitative correlations between ESI-MS measurements and solution properties. In this context, time dependences, concentration series, and counterion effects can serve as criteria that allow researchers assess if the gas-phase measurements correlate with the situation in the solution. Furthermore, we report developments that bridge the gap between gas-phase and solution-phase studies. We also describe predictions derived from ESI-MS that have been verified with solution-phase chemistry experiments.

Elusive Reaction Intermediates in Solution Explored by ESI‐MS: Reverse Periscope for Mechanistic Investigations

“…[7,11] Indeed, ionization processes which Just as periscopes allow as ubmarine to visually searchfor objects above the surface of the sea, in areversed periscope fashion electrospray mass spectrometry (ESI-MS) can analyzethe compounds at the gas phase/liquid phase interface for chemical entities whichmay exist in solution. The challenge is the identification and structural characterization of key elusive reaction intermediates in chemical transformations,i ntermediates whichare able to explain howc hemical processes occur.T his Minireview summarizes recent selected publications on the use of ESI-MS techniques for studying solution intermediates of homogeneous chemical reactions.…”

“…[8] Thepotential of this technique can be complemented and increased by MS n (n:m ultiple steps of product ion analysis) performance,ion mobility,ion spectroscopy, [9] and computational studies. [10,11] Herein we aim to review the most relevant and recent contributions on mechanistic studies of organic reactions, studies carried out by intercepting intermediates with ESI-MS.W ew ill also address the reliability of the various methods,a sw ell as their use in combination with the abovementioned techniques.…”

Gas-Phase Intramolecular Cyclization of Argentinated N-Allylbenzamides

“…To get a deeper insight into the intrinsic mechanisms without the interference of solvent effects or aggregation phenomena, researchers usually turn to mass spectrometry for help, especially electrospray ionization mass spectrometry (ESI-MS) [19][20][21][22]. With the high vacuum and feasible interface to the liquid phase, ESI-MS has long served as the gas-phase medium in which to form gaseous key ions and, hence, probe reaction mechanisms and establish intrinsic reactivity orders.…”

Study of the Transient Reactive Pd(IV) Intermediate in the Pd(OAc)2‐Catalyzed Oxidative Coupling Reaction System by Electrospray Ionization Tandem Mass Spectrometry

“…[23][24][25][26] Thus, the reactivity and structures of the reactive transient intermediates can then be further studied by MS/MS to provide clues for the study of reaction mechanisms. [27][28][29] The gas phase results of reaction system can reflect the system in liquid phase, [30,31] according to the gas phase results obtained by ESI-MS/MS, we can understand the process in the solution phase. Then we also synthesized the authentic Pd(IV) complex 3c•OAc and tried to ana-lyze it by ESI-MS/MS to further confirm the characteristic of the intercepted Pd(IV) transient intermediate in reaction solution.…”