Unveiling New Reactivities in Complex Mixtures: Synthesis of Tricyclic Pyridinium Derivatives

The discovery of new transformations drives the development of synthetic organic chemistry. While the main goal of synthetic chemists is to obtain the maximum yield of a desired product with minimal side product formation, meticulous characterization of the latter offers an opportunity for discovering new reaction pathways, alternative mechanisms, and new products. Herein, we present a case study on the discovery and development of a new chemical transformation using online mass spectrometry. This highly sensitive method enabled the discovery of a new reaction pathway in a catalyst-free cross-dehydrogenative coupling of 1,2,3,4-tetrahydroisoquinoline with acetone via peroxide intermediate, ultimately yielding a tricyclic pyridinium compound. Mass spectrometry was instrumental in detecting and identifying the structure of the pyridinium compound, initially formed as a trace byproduct, which allowed us to develop a general methodology for its exclusive formation.