Catalytic Atroposelective Nucleophilic Chlorination for the Synthesis of Chlorinated Atropisomers via Dual Photoredox/Nickel Catalysis

Abstract Axially chiral (hetero)biaryl halides represent important structural motifs in functional molecules and synthetic chemistry. While catalytic atroposelective halogenation offers a direct route to such scaffolds, existing approaches predominantly rely on electrophilic halogenating reagents. However, the use of stable and benign nucleophilic halogen sources─particularly for chlorination─remains underdeveloped. Herein, we report a dual photoredox-nickel-catalyzed atroposelective nucleophilic chlorination of racemic heterobiaryl triflates employing chloride ions as the nucleophile. This method affords axially chiral heterobiaryl chlorides in high yields with high enantioselectivity. The choice of photocatalyst governs the reaction pathway, enabling selective product formation through either kinetic resolution (KR) or dynamic kinetic asymmetric transformation (DyKAT). Furthermore, the resulting enantioenriched heterobiaryl chlorides undergo diverse transformations via C–Cl bond cleavage, yielding a range of functionalized heterobiaryl atropisomers and underscoring the synthetic utility of this methodology. Mechanistic investigations suggest the involvement of an energy transfer process and elucidate the distinct kinetic profiles associated with the KR and DyKAT pathways. This work advances catalytic atroposelective nucleophilic chlorination, establishes a photoredox/Ni-cocatalyzed asymmetric C–Cl coupling, and offers a flexible strategy for the enantioselective synthesis of halogenated atropisomers through switchable KR or DyKAT processes.