Mass Spec Discovery Platform Turns Up New Reactions

New chemical reactions are out there just waiting to be found, but the myriad possibilities need to be screened and optimized. A new reaction discovery and optimization platform called label-assisted laser desorption/ionization time-of-flight mass spectrometry accelerates the path from initial hit to a synthetically useful reaction, according to Sergey A. Kozmin of the University of Chicago and coworkers, who developed the process (Nat. Chem., DOI: 10.1038/nchem.1612). The method involves mixing a pyrene-labeled reactant with other reactants in the presence of various catalysts. The pyrene label enables photoionization of the reaction product for mass spec analysis. To demonstrate the approach, the team subjected a pyrene-labeled siloxy alkyne to 23 different reactants plus a control and 29 catalysts for a total of 696 experiments. The researchers identified two previously unknown benzannulation reactions. For example, reaction of the alkyne with isoquinoline N-oxide in the presence of a silver catalyst yielded an oxime product. They used the screening platform again to optimize the reaction and found that it works better with a gold catalyst.