8/26/2025 – Congratulations to Céline, Adrian, Karina, Sara, Dylan, Tom, and our collaborators at Janssen for their development of an N-regioselective alkylation method for azoles using alkenyl thianthreinum salts!

Azoles are important synthetic targets due to their diverse applications in areas ranging from human health to food security. Accordingly, access to N-functionalized azoles is an essential goal in modern synthetic chemistry. Surprisingly, however, the relied-upon azole N-alkylation strategies fundamentally limit the structural diversity of these important compounds that can be synthesized and studied. Here we introduce an approach to prepare a broad array of important but difficult-to-access N-alkyl azole compounds. We accomplish this through the introduction of a base-catalysed hydroazolation of readily accessible alkenylthianthrenium electrophiles. This strategy circumvents the classical challenge of azole alkylation regiocontrol through an unusual reversible C–N-bond-forming step that exploits the thermodynamic differences between azole N-alkylation isomers. This reaction furnishes a class of versatile azolothianthrenium building blocks that provides a general platform to investigate diverse N-alkyl azole molecules. More broadly, the distinctive approach outlined through this project is poised to impact the design and development of diverse regioselective alkylation reactions.