Molecular Framework Modification in Mass Spectrometry: Atom Exchange, Insertion, and Deletion.

The ionization and activation of molecules, as performed using mass spectrometry (MS), have long been known to induce unimolecular rearrangements in gas-phase ions and, in some cases, reorganization of the underlying skeletal framework. Here, we explore skeletal rearrangements occurring from the electrospray ionization process, including atom exchange, insertion, and deletion, within pre-existing ring systems. The Baeyer-Villiger oxidation, the Beckmann rearrangement, and the Favorskii rearrangement are longstanding organic reactions that are here explored in MS, alongside a unique sulfur-for-oxygen exchange reaction within a 2,4,6-triphenylpyrylium scaffold. MSn and high-resolution MS are used to examine four representative transformations of molecular frameworks. Reactions across the four types emphasize the fact that ESI-MS can be intrinsically reactive. Product assignments in each case are supported by exact-mass measurements, isotopic distribution analysis, and MS/MS comparison with authentic standards or by characteristic fragmentation behavior. Beyond demonstrating framework modifications in electrospray droplets, these results point to an expanded suite of reactions for reactive MS derivatization, as well as the development of future strategies for late-stage functionalization.