Highly Enantioselective Synthesis of Boron-Stereogenic Scaffolds via Bioinspired Bisphosphonium Salt-Catalyzed SNAr Reaction

Abstract

The enantioselective construction of boron-centered chirality remains a challenging topic in asymmetric catalysis. Although notable progress has been made in recent years, most existing strategies still rely on transition-metal catalysis, whereas organocatalytic approaches remain relatively scarce. Herein, we report an amide-based bisphosphonium salt-catalyzed asymmetric SNAr reaction that enables desymmetrically enantioselective C−O bond formation between prochiral α,α-dichloro BODIPY and phenolic nucleophiles, providing efficient access to boron-stereogenic BODIPY scaffolds. The strategy shows broad substrate scope and high stereocontrol (37 examples, up to 99% yield and >99% ee). Photophysical studies reveal that the resulting BODIPY derivatives display tunable optical properties and pronounced chiroptical activity. Mechanistic investigations indicate that cooperative hydrogen-bonding and ion-pair interactions between the catalyst and substrates generate a semienclosed chiral microenvironment, thereby enabling effective control over the stereoselectivity of the reaction. Our strategy transforms chiral BODIPYs from simple materials into highly diversifiable platform molecules bearing two synthetically valuable reactive sites, thereby unlocking synthetic versatility.