Chiral 3,4-H2-Dihydro-Monothiobinaphthol-Derived Bifunctional Catalysts: Design, Synthesis, and Application to Enantioselective Disulfuration of Aza[5]Helicenes

Abstract We herein report the design and synthesis of a class of 3,4-dihydro-monothiobinaphthol (3,4-H2-MTB)-derived bifunctional catalysts and their application in the asymmetric electrophilic C–H disulfuration of aza[5]helicenes. These catalysts feature a cooperative dual-activation motif: the thioether moiety acts as a Lewis base to activate the disulfurating reagent, while the phenolic hydroxyl group serves as a hydrogen-bond donor to engage the cocatalyst diphenyl phosphate. The reaction proceeds via a dynamic kinetic resolution mechanism, delivering a range of helically chiral aza[5]helicenes in good yields (up to 99%) and high enantioselectivities (up to 97% enantiomeric excess). The resulting enantioenriched products can be readily converted into helically chiral thiophenols, silyl sulfides, thioesters, and other derivatives. Mechanistic studies, including control experiments and density functional theory calculations, reveal that enantiocontrol arises from a synergistic network of noncovalent interactions including O–H···O hydrogen bonding, C–H···O interactions, and multiple C–H···π interactions facilitated by the 3,4-dihydro-binaphthyl framework. These features enable the in situ assembly of a chiral Lewis base/Brønsted acid catalytic manifold, which is instrumental in governing the observed enantioselectivity.