Exploring the Role of Halogen Bond Donors in the Thiourea‐Catalyzed Friedel–Crafts Alkylation Reaction

Abstract Halogen bonding (XB) has recently emerged as a powerful tool in organocatalysis, though asymmetric applications remain scarce. Here we report the first synergistic system combining a chiral thiourea and an inert XB donor. The iodine derivative enhances substrate activation via LP(I)→π*(C = C) interactions. Instead, a strong π–π interaction between the catalysts rules out direct thiourea activation. Applied to asymmetric Friedel–Crafts alkylation, iodoethynyl cocatalysts boost both reactivity and enantioselectivity. DFT calculations rationalize the crucial role of the XB donor, highlighting a new strategy to exploit non‐covalent interactions in asymmetric synthesis.