Indane-Based Chiral Aryl Chalcogenide Catalysts: Development and Applications in Asymmetric Electrophilic Reactions

CONSPECTUS: Asymmetric electrophilic reactions provide an ideal method for the construction of chiral molecules by incorporating one or more functional groups into the parent substrates under mild conditions. However, due to the issues of the reactivities of electrophilic species and the possible racemization of chiral intermediates as well as the restriction of the chiral scaffolds of chiral catalysts, many limitations remain in this field, such as the narrow scopes of substrates and electrophiles as well as the limited types of nucleophiles and reactions. To overcome the limitations in the synthesis of diversified chiral molecules, we developed a series of indane-based chiral amino aryl chalcogenide catalysts. These catalysts are easily prepared based on the privileged chiral indane scaffold. They can provide an appropriate H-bonding effect by varying the amino protecting groups as well as offer a proper Lewis basicity and steric hindrance by adjusting different substituents on the aryl chalcogenide motifs. These features allow for them to meet the requirements of reactivity and the chiral environment of the reactions. Notably, they have been successfully applied to various asymmetric electrophilic reactions of alkenes, alkynes, and arenes, expanding the field of electrophilic reactions. Using these catalysts, we realized the enantioselective CF3S-lactonization of olefinic carboxylic acids, enantioselective CF3S-aminocyclization of olefinic sulfonamides, desymmetrizing enantioselective CF3S-carbocyclization of gem-diaryl-tethered alkenes, enantioselective CF3S-oxycyclization of N-allylamides, enantioselective intermolecular trifluoromethylthiolating difunctionalization and allylic C-H trifluoromethylthiolation of trisubstituted alkenes, formally the intermolecular CF3S-oxyfunctionalization of aliphatic internal alkenes, intermolecular azidothiolation, oxythiolation, thioarylation of N-allyl sulfonamides, desymmetrizing enantioselective chlorocarbocyclization of aryl-tethered diolefins, enantioselective Friedel-Crafts-type electrophilic chlorination of N-allyl anilides, and enantioselective chlorocarbocyclization and dearomatization of N-allyl 1-naphthanilides. Additionally, the enantioselective electrophilic carbothiolation of alkynes to construct enantiopure carbon chirality center-containing molecules and axially chiral amino sulfide vinyl arenes and the electrophilic aromatic halogenation to produce P-chirogenic compounds can be accomplished. In these reactions, a bifunctional binding mode is proposed in the catalytic cycles, in which an acid-derived anion-binding interaction might exist and account for the high enantioselectivities of the reactions. In this Account, we demonstrate our achievements in asymmetric electrophilic reactions and share our thoughts on catalyst design, our understanding of asymmetric electrophilic reactions, and our perspectives in the field of chiral chalcogenide-catalyzed asymmetric electrophilic reactions. We hope that the experience we share will promote the design and development of other novel organocatalysts and new challenging reactions.

Automated summary

Asymmetric electrophilic reactions provide an ideal method for constructing chiral molecules, but there are many limitations. We have developed a series of chiral catalysts based on indane scaffold, which have been successfully used in various asymmetric electrophilic reactions, expanding the scope of electrophilic reactions.