Applications of electrospray ionization mass spectrometry in mechanistic studies and catalysis research.

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.