Catalytic Synthesis of Atropoisomers via Non‐Canonical Friedel‐Crafts Reactions

Abstract The Friedel‐Crafts reaction stands as a powerful synthetic tool for C−H functionalization of aromatic feedstocks, which is conventionally realized through electrophilic alkylation and acylation. The burgeoning interests in axially chiral compounds across diverse fields have spurred extensive exploration of this classic transformation for catalytic atroposelective synthesis. Consequently, the past decade has witnessed the rapid expansion of various non‐canonical Friedel‐Crafts reactions, including electrophilic arylation, alkenylation, halogenation, sulfenylation, and amination of aryl C−H bonds, thereby delving into new chemical spaces. A range of catalytic atroposelective synthetic methods have been devised for these significant arene C−H functionalization. This review provides a comprehensive overview of the cutting‐edge catalytic synthesis of atropoisomers through non‐canonical Friedel‐Crafts reactions, categorized into three parts based on the type of bond formation on the aromatics: C( sp 2 )−C( sp 3 ) bond formations, C( sp 2 )−C( sp 2 ) bond formations and C( sp 2 )−heteroatom bond formations. The richness of electrophiles and the modulation of atroposelectivity by diverse chiral organocatalysts, particularly chiral Brønsted acids, are elucidated. We anticipate that the repertoire of asymmetric Friedel‐Crafts reaction will continue to flourish and to be demonstrated in not only scientific researches but also industrial organic synthesis.