Autocatalysis in Eschenmoser Coupling Reactions

The Eschenmoser coupling reaction (ECR) of thioamides with electrophiles is believed to proceed via thiirane intermediates. However, little is known about converting the intermediates into ECR products. Previous mechanistic studies involved external thiophiles to remove the sulfur atom from the intermediates. In this work, an ECR proceeding without any thiophilic agent or base is studied by electrospray ionization-mass spectrometry. ESI-MS enables the detection of the so-far elusive polysulfide species Sn, with n ranging from 2 to 16 sulfur atoms, proposed to be the key species leading to product formation. Integrating observations from ion mobility spectrometry, ion spectroscopy, and reaction monitoring via flow chemistry coupled with mass spectrometry provides a comprehensive understanding of the reaction mechanism and uncovers the autocatalytic nature of the ECR reaction. Piecing the puzzle together. Mass spectrometry reveals the autocatalytic behavior of the Eschenmoser coupling reaction. Combining the results from ESI-MS coupled with various add-on methods, such as IR spectroscopy, ion mobility, or flow chemistry, leads to a comprehensive view of the reaction mechanism.+image