Atroposelective Pd(0)‐Catalyzed Direct Intermolecular C─H Arylation of Thiazole N ‐Oxides Provides Access to Heterobiaryls

ABSTRACT Despite the importance of heteroaryl atropisomers in medicinal chemistry and catalysis, straightforward access to these motifs via direct enantioselective C─H heteroaryl‐aryl coupling remains challenging. We report an enantioselective Pd(0)‐catalyzed arylation at the C4‐position of thiazole N ‐oxides, forging the critical atropochiral axis. A designer point‐ and axially chiral monodentate phosphine is instrumental to enable high reactivities along with tight stereocontrol. A broad range of substrate combinations is coupled in high enantioselectivities, including two different heteroarenes. The enantioenriched thiazole N ‐oxides are amenable to derivatizations around the substituents contributing to the stability of the chiral axis, including a reduction of the N‐ oxide moiety without racemization.