Nondirected, Site-Selective Arylation of Quinone Imine Ketals Derived from Arylamines: One-Pot Access to meta-Substituted Anilines

Herein, we develop a metal-free, nondirected, site-selective,one-potapproach to meta-arylation of arylamines. This Bronstedacid-catalyzed, direct C-C bond formation offers a broad substratescope and scalability and creates the ideal conditions for overridingthe conventional site-selectivity to furnish meta-substituted anilines. Additionally, the protocol applies to the meta-allylation of anilines and has been extended to affordlate-stage functionalization and synthesis of medicinally privilegedarylated diamines and densely functionalized anilines. The controlexperiments and density functional theory studies provide evidencefor the proposed mechanism and selectivity.

Automated summary

Here, we report a metal-free, nondirected, site-selective, and one-pot approach for the meta-arylation of arylamines. This method, catalyzed by a Bronsted acid, enables direct C-C bond formation and offers a wide range of substrate scope and scalability. It overrides the traditional site-selectivity to produce meta-substituted anilines. The protocol is also applicable for meta-allylation of anilines and can be extended to late-stage functionalization and synthesis of highly functionalized anilines and medicinally privileged arylated diamines. Control experiments and density functional theory studies support the proposed mechanism and selectivity.