Carbon Quaternization at the α-Position of Thiazoles: Iron-Catalyzed Hydroheteroarylation Using Unactivated Alkenes

Abstract Thiazoles are privileged N-heterocyclic scaffolds ubiquitous in FDA-approved drugs, yet their clinical utility can be compromised by oxidative metabolism at the heterobenzylic position. Inspired by the metabolic-blocking strategy used in dabrafenib development, herein we report an iron-catalyzed strategy for direct α-quaternization of (benzo)thiazoles using unactivated alkenes. Under the proposed pathway, alkene-derived carbon-centered radicals undergo regioselective C2 addition and oxidative rearomatization, providing α-quaternary products without heteroarene preactivation or stoichiometric Lewis acids, thereby enabling analogue diversification.